The breakthrough drug, which targets a small percentage of breast tumors, may be effective against more cancers, according to the latest study.

About 20% of women have breast cancers that are HER2 positive, meaning the tumor cells carry a protein on their surface that helps tumors grow faster. Herceptin (Trastuzumab), which binds to these proteins, blocks these cells from obtaining the nutrients they need to thrive, and in combination with other therapies, including chemotherapy or surgery, can dramatically reduce the recurrence rate of additional cancers.

Now researchers from the University of Michigan Comprehensive Cancer Center report in the journal Cancer Research that Herceptin may help women with HER2 negative tumors as well.

The revelation emerged from a study in which 174 women without HER2 receptors were miscategorized as having tumors with the protein, and were treated with Herceptin. Surprisingly, the treatment worked for them too. “These women essentially given Herceptin for a year by mistake. The surprising thing was when the data was analyzed, those women actually benefited more from the Herceptin than the women whose tumors were HER2 positive. Their reduction in recurrence was 50%, even though their tumors were so-called HER2 negative,” says study author Dr. Max Wicha, a professor of oncology and director of the University of Michigan Comprehensive Cancer Center.

Wicha and his team believe the results are driven by a small group of cancer stem cells that represent 1% to 5% of the cells in a tumor, but are largely responsible for spreading cancer to other tissues and locations. These cancer stem cells in many HER2 negative breast cancers may still make HER2, but not in enough quantities to register the cancer as HER2 positive. But because they are the cells responsible for metastases, or spreading the cancer, blocking their growth with Herceptin may lead to fewer recurrences for patients. “These are like the seeds of the cancer because these are cells that cause metastasis and have the unlimited potential to reproduce, whereas the other 90% to 95% of the cancer cells are essentially dead-end cells, so even though they form the bulk of the tumor, they don’t cause the spread,” says Wicha.

To test their theory, he and his colleagues bred mice with HER2 negative breast cancer and showed that HER2 positive stem cells in these animals spread to the bone, in the same way it does in humans. They also confirmed that Herceptin effectively knocks out these stem cells. “We think stem cells are being knocked out in women who have tiny microscopic metastasis in their bone marrow, and that’s why women benefit more from Herceptin when cancers are not HER2 amplified,” says Wicha. “If this is right, then more women may benefit from … [adding] Herceptin [to other cancer treatments].”

Even more exciting, says Wicha, the findings suggest that there may be two pathways that work simultaneously to promote tumor growth — one that is responsible for adding to the bulk of a tumor, and another that is focused on seeding new growths or recurrent cancers. Targeting and treating both processes at the same time may lead to better outcomes for patients, and possibly even cure more people of cancer. “Our work shows that we may be targeting two different cell populations. The shrinkage of the bulk tumors is driven by one set of pathways, whereas the stem cells may be driven by a different pathway,” he says. “You have to be able to target the pathways that regulate stem cells [to prevent recurrent growth]. If we knock those out, we think we will be able to cure many more patients.”

That would involve giving breast cancer patients, even those who are HER2 negative, Herceptin before metastases develop, to disable the cancer stem cells. “We hope that the next stage is to give these therapies in earlier stages of disease, because if our theories and mouse models are right, that’s how we are going to cure more patients. We can knock out the stem cells early before they establish very large metastases that are much harder to knock out,” he says. With a number of clinical trials already underway to test this theory, researchers will hopefully know how effective this strategy might be within three to five years.